The proposed research would continue investigations now in progress under NIH Grant AM-10956-12. The planned investigations will aim at inquiring into the pathogenesis of the lesions of the disease cystic fibrosis (CF) with a view toward identifying the cell type affected in sweat glands of the patients. Current projects concern correlated cytochemical and biochemical studies of the sweat gland in culture with the primary purpose of differentiating the possible role of humoral CF factors vs. inherent structural or biochemical defects in a cell with sweat gland. Sweat glands are being studied by ultrastructure and cytochemistry after periods of maintenance in explant under culture conditions. Cation fluxes are being investigated in sweat glands from normal and CF subjects maintained in culture in presence and absence of CF factors. Attempts are underway to culture epithelial cells from sweat glands. Inquiry is also proceeding into pathogenetic mechanism for development of abnormal megagranules in leukocytes, hepatocytes, renal tubules and other cells of beige mice with a disease analogous to the Chediak-Higashi syndrome of man. The contribution of accelerated autophagic processes related to increase plasmalemmal turnover to the development of some of the megagranules is under investigation. Differentiation of complex carbohydrates at the ultrastructural level will be undertaken with a view to characterizing both the type of glycoprotein-rich secretion and the luminal glycocayx in various epithelial cells of the stomach. Complex carbohydrates in the mitochondria of different cell types in the stomach will be localized by methods for ultrastructural demonstration of acidic, sulfated, and periodate-reactive glycoconjugates and the differences in mitochondrial complex carbohydrates, and the relation of differences in complex carbohydrates of mitochondria to specialized cell activities will be examined.